Isolation of 10 cyclosporine metabolites from human bile

Ten metabolites of cyclosporine were isolated from the ethyl ether extract of bile from four liver transplant patients receiving cyclosporine. Two of the metabolites were unique and previously unidentified. Liquid-liquid partitioning into diethyl ether with subsequent defatting with n-hexane was used for the initial extraction form bile. Separation of the individual metabolites (A-J) was performed using a Sephadex LH-20 column and a gradient high performance liquid chromatographic method. The molecular weights of the isolated metabolites were determined by fast atom bombardment/mass spectrometry. Gas chromatography with mass spectrometic amino acid analysis was also used to identify the amino acid composition and the hydroxylation position of metabolites A, B, C, D, and G. Proton nuclear magnetic resonance spectra were utilized to disinguish the chemical shifts of N-CH3 singlets and NH doublets of metabolites A, B, C, and D. Metabolites A, E, F, H, I, and J were reported previously in human urine and animal bile. Metabolites C and D are dihydroxylated compounds which cannot be clearly described as previously isolated compounds. Metabolites B and G are novel metabolites with a mass fragment which corresponded to a loss of 131 Da from the protonated molecular ion (MH+) in the fast atom bombardment/mass spectrometry, suggesting that the double bond in amino acid 1 has been modified. Metabolites B and G were primarily isolated from the bile of one of the liver transplant patients which contained abnormally high concentrations of these two metabolites. The method described is an efficient procedure for isolating milligram quantities of the major metabolites with greater than 95% purity

Transport of apolipoproteins A-I and A-II by human thoracic duct lymph

The daily transport of human plasma apolipoproteins A-I and A-II, triglyceride, and total cholesterol from the thoracic duct lymph into plasma was measured in 2 subjects before and 3 subjects after renal transplantation. Lymph triglyceride transport was ~83% of the daily ingested fat loads, whereas lymph cholesterol transport was consistently greater than the amount of daily ingested cholesterol. Lymph apolipoprotein transport significantly (P < 0.05) exceeded the predicted apolipoprotein synthesis rate by an average of 659±578 mg/d for apolipoprotein A-I and 109±59 mg/d for apolipoprotein A-II among the 5 subjects. It is estimated that 22-77% (apolipoprotein A-I) and 28-82% (apolipoprotein A-II) of daily total body apolipoprotein synthesis takes place in the intestine. Lymph high density lipoprotein particles are mostly high density lipoprotein(2b) and high density lipoprotein(2a) and have a greater overall relative triglyceride content and a smaller relative cholesteryl ester content when compared with homologous plasma high density lipoproteins. The major quantity of both lymph apolipoprotein A-I (81±8%) and apolipoprotein A-II (90±11%) was found within high density lipoproteins with almost all of the remainder found in chylomicrons and very low density lipoproteins. The combined results are consistent with a major contribution of the intestine to total body synthesis of apolipoprotein A-I and apolipoprotein A-II. An important role of lymph in returning filtered apolipoprotein to plasma in association with high density lipoproteins is proposed. Accompanying the return of filtered apolipoprotein to the plasma is a probable transformation, both in size and composition, of at least some of the lymph high density lipoprotein(2b) and high density lipoprotein(2a) particles into high density lipoprotein3

Net histocompatibility ratios (NHR) for clinical transplantation.

In this study, the histocompatibility match of a group of patients treated at least one and a half years ago was calculated by a modification of the net histocompatibility ratio (NHR) formula of Rapaport and Dausset.1 Correlations were then made with the outcome as judged by patient and kidney survival, homograft function, the magnitude of maintenance immunosuppression, and the extent of histopathologic abnormalities in the transplants

Negative time delay for wave reflection from a one-dimensional semi-harmonic well

It is reported that the phase time of particles which are reflected by a one-dimensional semi-harmonic well includes a time delay term which is negative for definite intervals of the incoming energy. In this interval, the absolute value of the negative time delay becomes larger as the incident energy becomes smaller. The model is a rectangular well with zero potential energy at its right and a harmonic-like interaction at its left.Comment: 6 pages, 5 eps figures. Talk presented at the XXX Workshop on Geometric Methods in Physics, Bialowieza, Poland, 201

Intestinal transplantation in composite visceral grafts or alone

Under FK 506-based immunosuppression, the entire cadaver small bowel except for a few proximal and distal centimeters was translated to 17 randomly matched patients, of whom two had antigraft cytotoxic antibodies (positive cross-match). Eight patients received the intestine only, eight had intestine in continuity with the liver, and one received a full multivisceral graft that included the liver, stomach, and pancreas. One liver-intestine recipient died after an intestinal anastomotic leak, sepsis, and graft- versus-host disease. The other 16 patients are alive after 1 to 23 months, in one case after chronic rejection, graft removal, and retransplantation. Twelve of the patients have been liberated from total parenteral nutrition, including all whose transplantation was 2 months or longer ago. The grafts have supported good nutrition, and in children, have allowed growth and weight gain. Management of these patients has been difficult and often complicated, but the end result has been satisfactory in most cases, justifying further clinical trials. The convalescence of the eight patients receiving intestine only has been faster and more trouble free than after liver-intestine or multivisceral transplantation, with no greater difficulty in the control of rejection